Ahmed Abu-Zaid, Jie Fang, Hongjian Jin, Shivendra Singh, Prahalathan Pichavaram, Qiong Wu, Heather Tillman, Laura Janke, Wojciech Rosikiewicz, Beisi Xu, Lee-Ann Van De Velde, Yian Guo, Yimei Li, Noha A M Shendy, Ian M Delahunty, Zoran Rankovic, Taosheng Chen, Xiang Chen, Kevin W Freeman, Mark E Hatley, Adam D Durbin, Peter J Murray, Andrew J Murphy, Paul G Thomas, Andrew M Davidoff, Jun Yang
Neuroblastoma with MYCN amplification (MNA) is a high-risk disease that has a poor survival rate. Neuroblastoma displays cellular heterogeneity, including more differentiated (adrenergic) and more primitive (mesenchymal) cellular states. Here, we demonstrate that MYCN oncoprotein promotes a cellular state switch in mesenchymal cells to an adrenergic state, accompanied by induction of histone lysine demethylase 4 family members (KDM4A-C) that act in concert to control the expression of MYCN and adrenergic core regulatory circulatory (CRC) transcription factors...
March 19, 2024: Cell reports medicine